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Tuesday, March 7, 2017

New Technique Uses Immune Cells to Deliver Anti-Cancer Drugs

Pennsylvania: Many
groups are working to discover new, safer ways to deliver drugs that
fight cancer to the tumor without damaging healthy cells. Others are
finding ways to boost the body’s own immune system to attack cancer
cells. For the first time, researchers at Penn State have combined the
two approaches by conjugating biodegradable polymer nanoparticles
encapsulated with chosen cancer-fighting drugs into immune cells to
create a smart, targeted system to attack cancers of specific types.
“The traditional way to deliver drugs to tumors is to put the drug
inside some type of nanoparticle and inject those particles into the
bloodstream,” said Jian Yang, professor of biomedical engineering, Penn
State. “Because the particles are so small, if they happen to reach the
tumor site they have a chance of penetrating through the blood vessel
wall because the vasculature of tumors is usually leaky.”
The odds of interacting with cancer cells can be improved by coating
the outside of the nanoparticles with antibodies or certain proteins or
peptides that will lock onto the cancer cell when they make contact.
However, this is still a passive drug delivery technology. If the
particle does not go to the tumor, there is no chance for them to bind
and deliver the drug.
Yang and Cheng Dong, department head and distinguished professor of
biomedical engineering, wanted a more active method of locating drugs to
the cancer wherever it was located, whether circulating in the blood,
or in the brain or in any of the other organs of the body.

“I have 10 years of working in immunology and cancer,”
Dong said. “Jian is more a biomaterials scientist. He knows how to make
the nanoparticles biodegradable. He knows how to modify the particles
with surface chemistry, to decorate them with peptides or antibodies.
His material is naturally fluorescent, so you can track the particles at
the same time they are delivering the drug, a process called
theranostics that combines therapy and diagnostics. On the other hand, I
study the cancer microenvironment, and I have discovered that the
microenvironment of the tumor generates kinds of inflammatory signals
similar to what would happen if you had an infection.”

Immune cells, which were built to more respond to inflammatory
signals, will be naturally attracted to the tumor site. This makes
immune cells a perfect active delivery system for Yang’s nanoparticles.
The same technology is also likely to be effective for infectious or
other diseases, as well as for tissue regeneration Dong said.
In the first proof of their technology, the two research groups
targeted circulating melanoma cells. In a paper published in the current
online issue of the journal Small, titled “Immune Cell-Mediated
Biodegradable Theranostic Nanoparticles for Melanoma Targeting,” the
researchers report the use of a novel biodegradable and photoluminescent
poly (lactic acid) (BPLP-PLA) nanoparticle, loaded with
melanoma-specific drugs with immune cells as the nanoparticle carriers.
They showed that the immune cells could bind to the melanoma cells under
shear stress conditions similar to those in the bloodstream. These
experiments were all performed outside the body. Next they intend to
perform studies in animal models and in solid tumors.
“This is the first study and is just to show that the technology
works,” Dong said. “This study is not about curing melanoma. There are
probably other ways to do that. We used melanoma cells to validate the
approach.”
In addition to corresponding authors Cheng Dong and Jian Yang,
co-lead authors are Zhiwei Xie, postdoctoral scholar in Yang’s group,
Yixue Su, a master’s student in Yang’s group, and Gloria Kim, a Ph.D.
student advised by both Yang and Dong. Other contributors are Erhan
Selvi, an undergraduate researcher in Dong’s lab, Chuying Ma, a Ph.D.
student in Yang’s lab, Virginia Aragon-Sanabria, a Ph.D. student in
Dong’s lab, and Jer-Tsong Hsieh, from the University of Texas
Southwestern Medical Center.
The research was supported by the National Institutes of Health and
the National Science Foundation. Both Dong and Yang are faculty in Penn
State’s Dept. of Biomedical Engineering, Materials Research Institute,
and Huck Institutes of the Life Sciences.
Contacts: Dr. Jian Yang, jxy30@psu.edu; Dr. Cheng Dong, cxd23@psu.edu